Nucleic acid-templated reactions leading to a fluorescent product represent an attractive strategy for the detection and imaging of cellular nucleic acids. Herein we report the use of a Staudinger reaction to promote the reduction of profluorescent azidorhodamine. The use of two cell-permeable GPNA probes, one labeled with the profluorescent azidorhodamine and the other with trialkylphosphine, enabled the detection of the mRNA encoding O-6-methylguanine-DNA methyltransferase in intact cells.

A new orthogonal solid-phase iterative strategy is proposed for the synthesis of sequence-coded polymers. This approach relies on the use of two successive chemoselective steps: (i) phosphoramidite coupling, and (ii) radical-radical coupling. These repeated steps can be performed using two different types of building blocks, i.e. a phosphoramidite monomer that also contains an alkyl bromide and a hydroxy-functionalized nitroxide. The phosphoramidite and the hydroxy group are reacted in step (i), thus leading to a phosphite that is oxidized in situ into a phosphate bond. The alkyl bromide is activated by copper bromide in step (ii) to afford a carbon-centered radical that is spin-trapped in situ by the nitroxide. The iterative repetition of these steps allow synthesis of uniform polymers, as evidenced by high-resolution electrospray mass spectrometry. Moreover, binary information could be easily implemented in the polymers using different types of phosphoramidite monomers in step (i). Interestingly, it was found that the formed information-containing polymers are very easy to sequence by tandem mass spectrometry due to the presence of easily cleavable alkoxyamine bonds formed in step (ii).